Kinetic analysis of striatal clearance of exogenous dopamine recorded by chronoamperometry in freely-moving rats.

Abstract:

:Previously, we developed technology that coupled high-speed chronoamperometry with microejections of dopamine (DA) to measure DA clearance in the brains of freely-behaving rats. Here, by varying the ejection volumes of DA across a 200-fold difference, the kinetics of striatal clearance were analyzed as a function of time and DA volume from 289 chronoamperometric signals (n=20 rats). Each DA clearance trace was fitted to a first-order exponential decay function to determine the rate constant for DA clearance (k). Additionally, the apparent Michaelis-Menten V(max) and K(m) kinetic constants were determined in freely-moving rats, enabling quantitative comparison of our values with other models of reuptake. The first-order rate constant for DA clearance, which reflects the V(max)/K(m) ratio or clearance efficiency, did not vary significantly when small volumes of DA were ejected resulting in peak DA signal amplitudes (A(max)) of <5 microM. However, following nomifensine-induced DAT inhibition, A(max) was increased and k was attenuated simultaneously with behavioral activation; and A(max) and behavior remained elevated beyond the initial period. Our results indicate that the analysis of kinetic parameters from chronoamperometric DA signals may be useful for investigating drug-induced regulation of DAT kinetics in relation to the behavior of freely-moving rats.

journal_name

J Neurosci Methods

authors

Sabeti J,Adams CE,Burmeister J,Gerhardt GA,Zahniser NR

doi

10.1016/s0165-0270(02)00229-7

subject

Has Abstract

pub_date

2002-11-15 00:00:00

pages

41-52

issue

1

eissn

0165-0270

issn

1872-678X

pii

S0165027002002297

journal_volume

121

pub_type

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